Anti-osteoarthritis effect of a combination treatment with human adipose tissue-derived mesenchymal stem cells and thrombospondin 2 in rabbits

BACKGROUND Osteoarthritis(OA),a chronic age-related disease characterized by the slowly progressive destruction of articular cartilage,is one of the leading causes of disability.As a new strategy for treatment of OA,mesenchymal stem cells(MSCs)have the potential for articular cartilage regeneration.Meanwhile,thrombospondin 2(TSP2)promotes the chondrogenic differentiation of MSCs.AIM To investigate whether TSP2 induces chondrogenic differentiation of human adipose-derived MSCs(hADMSCs)and potentiates the therapeutic effects of hADMSCs in OA rabbits.METHODS We investigated the chondrogenic potential of TSP2 in hADMSCs by analyzing the expression of chondrogenic markers as well as NOTCH signaling genes in normal and TSP2 small interfering RNA(siRNA)-treated stem cells.Anterior cruciate ligament transection surgery was performed in male New Zealand white rabbits,and 8 wk later,hADMSCs(1.7×10^6 or 1.7×10^7 cells)were injected into the injured knees alone or in combination with intra-articular injection of TSP2(100 ng/knee)at 2-d intervals.OA progression was monitored by gross,radiological,and histological examinations.RESULTS In hADMSC culture,treatment with TSP2 increased the expression of chondrogenic markers(SOX9 and collagen Ⅱ)as well as NOTCH signaling genes(JAGGED1 and NOTCH3),which were inhibited by TSP2 siRNA treatment.In vivo,OA rabbits treated with hADMSCs or TSP2 alone exhibited lower degree of cartilage degeneration,osteophyte formation,and extracellular matrix loss 8 wk after cell transplantation.Notably,such cartilage damage was further alleviated by the combination of hADMSCs and TSP2.In addition,synovial inflammatory cytokines,especially tumor-necrosis factor-α,markedly decreased following the combination treatment.CONCLUSION The results indicate that TSP2 enhances chondrogenic differentiation of hADMSCs via JAGGED1/NOTCH3 signaling,and that combination therapy with hADMSCs and TSP2 exerts synergistic effects in the cartilage regeneration of OA joints.

Comparative effects of plant oils and trans-fat on blood lipid profiles and ischemic stroke in rats

Since plant oils are believed to be better than animal fats for cerebrovascular and cardiovascular diseases, the effects of various plant oils and trans-fat on blood lipid profiles and ischemic stroke were investigated. Sprague- Dawley rats were fed a diet containing the oils or trans-fat, and then body weights, blood lipids, and effects on brain infarction and physical dysfunction induced by middle cerebral artery occlusion （MCAO） were analyzed. All the oils and trans-fat, except perilla oil, significantly increased body fats and body weight gain. Sesame oil and trans-fat specifically increased blood cholesterols and triglycerides, respectively, while perilla oil decreased both cholesterols and triglycerides. Perilla oil not only attenuated cerebral infarction, but also restored locomotor activity and rota-rod performances of MCAO rats. It is suggested that perilla oil among oils and fats could be the first choice to reduce the risk of metabolic syndrome and ischemic stroke.

Hydrogen-enriched water eliminates fine particles from the lungs and blood by enhancing phagocytic activity

Particulate matters（PM） are one of the major body burdens leading to diseases. We investigated the capacities of a hydrogen-enriched water（HW） eliminating carbon nanoparticles（CNP） and carbon microparticles（CMP） from the lungs and blood, respectively. In CNP-elimination test, rats were orally administered with purified water（PW） or HW（10 or 30 mL/kg/day） for 10 weeks. At the time point of 4 weeks, the rats were challenged with intratracheal instillation of CNP（4 mg）. CNP accumulated in the airways and alveoli, and induced inflammatory lesions. Such pneumoconiosis was markedly improved by feeding HW, while PW was ineffective. CNP-induced pneumoconiosis caused systemic hematological alterations, decreasing major inflammatory cells, but markedly increasing eosinophils,indicative of an allergic reaction, which were attenuated by treatment with HW. Such PM-eliminating and antiallergic effects of HW reduced body burden as confirmed from the facilitated recovery of body and lung weights. In CMP-clearance test, mice were orally administered with PW or HW for 7 days, and intravenously injected with CMP（300 mg/kg）. CMP was rapidly eliminated from the blood in HW-fed mice. Indeed, the phagocytic indices increased to 3.5 and 6.7 folds at 10 and 30 mL/kg of HW, in comparison with a negligible effect of PW. As a mechanism study,only HW significantly inhibited lipid peroxidation in vitro Fenton reaction-mediated ·OH-generating system.Collectively, the results indicate that HW not only effectively eliminated PM from the lungs and blood by enhancing phagocytic activity, but also attenuated the lung injuries by inhibiting lipid peroxidation.

Effects of a soybean milk product on feto-neonatal development in rats

Since estrogenic pollutants and phytoestrogens can cause the disorder of the reproductive system, the effects of a soybean milk product（Vegemil^（？） containing 162 ppm isoflavones） on the feto-neonatal development, including male reproductive function, were investigated. Pregnant rats were fed the soybean milk（5% or 100% in drinking water）from gestational day（GD） 6 to parturition or to post-natal day（PND） 56. Specifically, the rats were divided into 4 groups： the control group（drinking water）, the GD5% group（5% soybean milk during only the GD period）, the GDPND5% group（5% soybean milk during the GD and PND periods）, and the GD-PND100% group（100% soybean milk instead of water during the GD and PND periods）. During the gestational, lactational, and developmental periods, the reproductive and developmental parameters of dams and offspring were observed. Feeding soybean milk did not affect the birth and physical development of both male and female offspring. At PND57, the weights of the testes and epididymides of F1 males significantly increased by feeding a high concentration of the soybean milk（GDPND100%）. In addition, feeding of the soybean milk during both the GD and PND periods（GD-PND5% and GDPND100%） enhanced the sperm counts and motility. The results indicate that soybean milk is safe for embryos,fetuses, and offspring, and improves the post-generational development of male reproductive function.